Infectious diseases caused by pathogenic microorganisms, such as bacteria, viruses, parasites or fungi can be spread directly or indirectly from one person to another. Zoonotic diseases are infectious diseases of animals that can cause disease when transmitted to humans (WHO). For decades, infectious diseases have represented a global health problem responsible for the deaths of millions of people. Today, hundreds of antibiotics are available for the treatment of different infectious diseases. However, one of the major problems facing infection treatment is the increasing resistance particularly of bacteria against many antibiotics, forcing physicians to combine two or even more antibiotics to fight bacterial infections. In addition to bacterial resistance, the poor permeability of some antibiotics through biological membranes is a limiting factor for their effective use, i.e. aminoglycosides, a broad spectrum class of antibiotics comprising molecules such as e.g. streptomycin, amikacin, neomycin, netilimicin, tobramycin and gentamicin. All these molecules exhibit poor permeability profiles through biological membranes and a narrow therapeutic index, associated with notable toxicity, meaning that their use is largely limited to the treatment of extracellular infections. Even if clinical medicine has an extremely long list of different pharmaceutical products at its disposal, the main challenge for scientists and physicians lies in the specificity of these pharmaceutical compounds, and their ability to selectively reach their targets. Normally, drugs are systemically distributed, but to reach the target zone they have to cross many other organs, cells, and intracellular compartments, where they can be partially inactivated. Moreover, side effects, related to drug accumulation and toxicity of therapeutic drugs are still major concerns in medical practice. Therefore, scientists have developed new strategies to make it possible to target drugs towards specific cells, tissues or organs. Most of these strategies are based on using suitable carriers, such as serum proteins, synthetic polymers-based particles, microspheres and liposomes, which can be targeted to specific areas in a variety of different ways, such as immunolabeling. Among these carriers, liposomes are considered as a promising drug delivery system for carrying drugs to the site of action and controlling the release of these drugs at a predetermined rate. Liposomes in themselves are biocompatible and biodegradable (weakly immunogenic inducing no antigenic or pyrogenic reactions) and possess a limited intrinsic toxicity. They provide the possibility to entrap water-soluble pharmacological agents in their internal aqueous compartment or inter bilayer spaces if they are multilamellar vesicles and water-insoluble agents within their lipid membrane(s). They also provide the protection for the encapsulated pharmacological agents from the external environment. Liposomes can be formulated as a solution, aerosol, in a semisolid form or dry vesicular powder (pro-liposomes for reconstitution). This gives liposomes the opportunity to be administered via a number of different routes, including the oral, topical, pulmonary, nasal, ocular, subcutaneous, intramuscular and intravenous routes. Liposomes can encapsulate both micro and macromolecules. From a pharmacological point of view, liposomes have the ability to modify the pharmacokinetic and pharmacodynamic properties of drugs by increasing their efficacy and therapeutic index, and by reducing drug toxicity and related side effects. Liposomes offer the opportunity to deliver pharmacological agents into cells or even into individual cellular compartments. They provide the possibility to be used in passive targeting and they also offer the flexibility to be coupled with site-specific ligands to achieve active targeting.
In recent years, the idea of using bacterial surface protein invasin in targeted oral drug delivery was considered by some researchers. Invasin was used to mediate gene delivery, where a fragment of invasin was attached to non-specific DNA-binding domains (SPKR). This complex was able to bind β1-interin receptors. Approaches attaching peptide tags on nanoparticles to initiate or enhance nanoparticles uptake by mammalian cells have significantly increased over the past years. Yet, impact on clinical praxis remains disappointing. The present inventors have surprisingly found that invasin decorated carriers can be used as a “bacteriomimetic” delivery system. Invasin was used as model bacterial protein to coat liposomes to resemble the Gram-negative bacterium Yersinia pseudotuberculosis. Using this model system the successful design of bacteriomimetic/bioinvasive delivery system mimicking invasive bacteria expressing internalization factors integrated in the outer membrane of their cell envelope has been successfully shown. The present invention therefore, provides a new formulation which can be used to enhance the cellular permeability of hydrophilic drugs and reduce its toxicity by encapsulation into nanoparticles. Thus, the resulting formulation can be used for the treatment of intracellular infections reaching bacteria sequestering in intracellular compartments.